VEGFR2 Antibody CDR Engineering for Angiogenesis Inhibition
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Solution Overview
Problem
Current antibodies targeting VEGFR2 for inhibiting angiogenesis, such as ramucirumab, have limitations in efficacy and specificity, necessitating the development of an antibody with enhanced binding ability and inhibitory effects on endothelial cell growth and angiogenesis.
Innovation Solution
An antibody with specific heavy and light chain variable region CDR amino acid sequences, including CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3, is developed, which binds to VEGFR2 with high affinity, inhibiting endothelial cell proliferation and angiogenesis, and is used in a pharmaceutical composition for treating angiogenesis-related diseases.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If ramucirumab is used to target VEGFR2 for inhibiting angiogenesis, then angiogenesis-related diseases can be treated, but the efficacy and specificity are limited
Solution Approach 1:
The patent applies parameter changes by modifying the antibody structure through engineered CDR sequences. The heavy chain CDRs (CDRH1: SEQ ID NO: 1, CDRH2: SEQ ID NO: 2, CDRH3: SEQ ID NO: 3) and light chain CDRs (CDRL1: SEQ ID NO: 4, CDRL2: SEQ ID NO: 5, CDRL3: SEQ ID NO: 6) are specifically designed with optimized amino acid sequences to enhance binding affinity and specificity to VEGFR2, thereby improving both efficacy and specificity simultaneously
Solution Approach 2:
The patent applies local quality by optimizing specific regions of the antibody molecule. The complementarity determining regions (CDRs) are locally engineered with specific amino acid sequences to enhance binding to particular epitopes on VEGFR2, while the rest of the antibody structure maintains its general framework. This localized optimization allows the antibody to achieve superior specificity and efficacy compared to conventional antibodies
2Productivity
If conventional antibodies are used to target VEGFR2, then angiogenesis can be inhibited, but the binding ability and inhibitory effects are insufficient
Solution Approach 1:
The patent employs parameter changes by optimizing the biochemical parameters of the antibody-antigen interaction. The engineered CDR sequences are designed to maximize hydrogen bonding, van der Waals interactions, and other molecular forces between the antibody and VEGFR2, resulting in enhanced binding affinity (lower KD value) and improved inhibitory efficacy in blocking VEGF-VEGFR2 interaction
Solution Approach 2:
The patent applies mechanics substitution by replacing conventional antibody structures with engineered variants that utilize optimized molecular interactions. The engineered CDRs create more effective molecular recognition and binding mechanisms through precisely positioned amino acid residues that form optimal interaction networks with VEGFR2, thereby enhancing binding ability and inhibitory effects
Data Source
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AI summary
The present invention relates to a novel antibody against VEGFR2 for use in the prevention or treatment of macular degeneration and cancer, which are angiogenesis-related diseases. The antibody of the present invention is an antibody which specifically binds to VEGFR2 which is overexpressed in vascular endothelial cells. The antibody of the present invention has very low homology compared to the CDR sequences of conventional VEGFR2 target antibodies , and thus is unique in its sequence. Since the antibody of the present invention, when treated alone, has the ability to inhibit vascular endothelial cell growth equivalent to that of ramucirumab which is conventionally used, it is very effective to prevent or treat angiogenesis-related diseases.